Effects of extracellular K+ and Ca2+ on membrane potential, contraction and 86Rb+ efflux in guinea-pig mesotubarium.

The effects of varying extracellular concentrations of K+ and Ca2+ [K+]o and [Ca2+]o on force development and membrane potential were investigated in the guinea-pig mesotubarium. At [K+]o up to 40 mM, spontaneous action potentials were present, while higher [K+]o gave sustained contractures at a stable membrane potential (-24 to -12 mV for [K+]o from 60 to 120 mM). Tension decreased successively with increasing [K+]o from 30 to 120 mM. The relaxing potency of the dihydropyridine Ca2+ antagonist, felodipine, increased as the membrane was depolarized with increasing [K+]o and action potentials ceased. These results are compatible with the existence of Ca2+ channels showing voltage-dependent affinity with dihydrophyridines. Increasing [Ca2+]o from 2.5 to 10 mM caused membrane hyperpolarization by about 11 mV and was accompanied by a lower frequency of spontaneous contractions and a longer duration of the relaxation between contractions. 86Rb+ efflux measurements in 60 mM K+ in the absence and presence of felodipine revealed a Ca2(+)-dependent component of the voltage-activated efflux. In normal solution (5.9 mM K+), efflux in the presence of felodipine was similar to the minimal value during normal spontaneous activity. The results indicate regulation of the permeability of K+ channels by the intracellular Ca2+ concentration ([Ca2+]i) and suggest participation of such channels in the generation of the regularly occurring bursts of action potentials characteristic of spontaneous activity in the mesotubarium.